Variant 8-22148444-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_139278.4(LGI3):c.1363C>A(p.Arg455Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,612,104 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LGI3
NM_139278.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.66

Variant links:

Genes affected

LGI3 (HGNC:18711): (leucine rich repeat LGI family member 3) Predicted to enable catalytic activity. Predicted to be involved in regulation of exocytosis. Predicted to be located in extracellular region. Predicted to be active in synaptic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

LGI3 links:

LGI3 (HGNC:):

LGI3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGI3	NM_139278.4 linkuse as main transcript	c.1363C>A	p.Arg455Ser	missense_variant	8/8	ENST00000306317.7	NP_644807.1	Q8N145-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LGI3	ENST00000306317.7 linkuse as main transcript	c.1363C>A	p.Arg455Ser	missense_variant	8/8	1	NM_139278.4	ENSP00000302297.2	Q8N145-1
LGI3	ENST00000424267.6 linkuse as main transcript	c.1291C>A	p.Arg431Ser	missense_variant	7/7	1		ENSP00000399121.2	Q8N145-2
LGI3	ENST00000520124.5 linkuse as main transcript	n.2806C>A		non_coding_transcript_exon_variant	6/6	1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459954

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726340

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.1363C>A (p.R455S) alteration is located in exon 8 (coding exon 8) of the LGI3 gene. This alteration results from a C to A substitution at nucleotide position 1363, causing the arginine (R) at amino acid position 455 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.039

T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.0

L;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.40

N;N

REVEL

Uncertain

0.44

Sift

Benign

0.82

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.96

D;.

Vest4

0.60

MutPred

0.63

Loss of MoRF binding (P = 0.066);.;

MVP

0.89

MPC

0.62

ClinPred

0.93

GERP RS

5.2

Varity_R

0.16

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over